Viral interference: A. Intrinsic interference - To study and define (a) the spectrum of viruses that act as inducers of this class of interference, (b) the viruses sensitive to such interference, and (c) the molecular basis of the interference - using as a working hypothesis the concept of heterologous polymerase molecules, or their product(s) as regulators of viral (and cellular) RNA synthesis. B. Interferon-mediated interference: To study and define (a) optimal and regulatory conditions for the induction of interferon - inducing an analysis of cell "aging" effects, (b) the molecular basis of interferon action based on evidence that the virion-bound transcriptase of Vesicular stomatitis virus is inhibited by the interferon system - in vivo, and in vitro. Cellular and viral regulation of virus replication: (1) To study and define the mechanism underlying the inhibition of virus replication (a) in mitotic cells and (b) in guanidine-treated cells. (2) To quantitate cell killing by viruses with altered genomic function, and (3) detect, assay and define viruses in noncytopathic-cell relationships. Membrane modification in normal and virus-infected cells: To study (a) the cellular programming responsible for the well-defined pattern whereby viral-induced and normal cell macromolecules newly synthesized in the cytoplasm gain access to, and become incorporated in the plasma membrane, and (b) the effect of altered cell surfaces - as in the transformed cell, on these reactions.